The mouse is the predominant model organism in research: nearly 60% of all animals used for experimental purposes in Europe are mice. Breeding efficiency is often hampered by reproductive problems and high pup mortality is one of the main issues. Despite the size of the problem, there has been very little scientific research into the phenomenon and its underlying factors. In most cases, neither the direct cause of death nor the events leading up to it are known.
Of the 11.5 million animals used in the European Union in 2011, 60% were mice. To compensate for an early litter loss of 25% an estimated 1.7 million animals must be bred every year on the European level.
Often the whole litter is lost, thus seriously affecting the logistics of animal breeding with subsequent economic consequences of having to keep larger numbers of breeding animals. High pup mortality is cause for particular concern as this is also an animal health and welfare issue.
Literature reports pup mortalities varying from <10% to 49% for the commonly used C57BL/6 strain. However, it is difficult to get a good picture of perinatal mortality in contemporary research animal facilities. Pup mortality is only occasionally reported in papers where breeding was part of the experimental protocol, and very few papers exist where mortality was systematically studied.
In the first large multi-site study under practice conditions we showed that mortality varies greatly between facilities and is substantially larger than reference data. In data from 35,000 litters of C57BL/6 mice we found 39% preweaning mortality in one facility and 14% in the other, whereas reference data is 8%.
Mice’ nocturnal and nestbuilding nature, and the fact that dead pups are often eaten by the progenitors make mortality challenging to detect and quantify, further complicated by the standard practice of limiting inspection of periparturient females to what can be seen without opening the cage. Pups are often not counted until the first cage change, up to 2 weeks postpartum. We know from our several experiments that most pups die on days 0-3 postpartum, i.e. earlier than the first pup count in many breeding facilities. It is likely that many animal facilities underestimate mortality because newborn pups are missed.
We are using a combination of ethology, epidemiology, data science and pathology in our research into neonatal pup mortality.
Sophie Brajon / Anna Olsson